Stimulation of pulmonary sympathetic and parasympathetic nerves in anesthetized animals leads to changes in lung function by altering ventilation-perfusion relationships. How the autonomic nervous system effects changes in lung function are poorly understood. Certainly, combination of factors must be considered including changes in pulmonary blood flow, alterations in mucous production or release, and changes in the tone of airway smooth muscle. The regulation and behavior of airway smooth muscle is the area in which we have a primary interest and our principal goals are to: 1) determine the neural control of airway smooth muscle, 2) investigate the modulation of the neuroeffector response of airway smooth muscle by certain pharmacological agents, and 3) determine the nature of receptors on airway smooth muscle cells. The effects of electrical stimulation and various exogenous agents on smooth muscle tone in the trachea, large intrapulmonary airways, and small intrapulmonary airways will be compared in in vitro tissue bath experiments. Canine airways will be studied throughout the project three year period with experiments being expanded to include human airways as various methods of procedure are perfected. We plan a multidisciplinary approach involving physiological, pharamacological and histological studies. Results from the proposed experiments will clarify the role of the autonomic nervous system in modulating airway caliber at different levels of the tracheobronchial tree.